Christopher Devin Malone MD, Presenter: Nothing to Disclose

Emilia Sue Olson MD, PhD, Abstract Co-Author: Nothing to Disclose

Robert Frederick Mattrey MD, Abstract Co-Author: Nothing to Disclose

Nadia Nashi, Abstract Co-Author: Nothing to Disclose

Tao Jiang PhD, Abstract Co-Author: Nothing to Disclose

Leslie Ellies, Abstract Co-Author: Nothing to Disclose

Roger Y. Tsien MD, Abstract Co-Author: Research Consultant, Avelas Biosciences, Inc Stockholder, Avelas Biosciences, Inc

Quyen Nguyen, Abstract Co-Author: Nothing to Disclose

Matrix metalloproteinases-2 and -9 (MMP-2/-9) are upregulated in many aggressive tumors. We aimed to compare the tumor detection performance of a standard Gd-chelate to that of Gd-loaded MMP-2/-9 activatable cell-penetrating peptide dendrimers (ACPPD-Gd) using a murine tumor model representative of aggressive triple-negative breast cancer with 3T MR.

Using a protocol approved by the Institutional Animal Care and Use Committee, 2 of 4 inguinal breast fat pads of 16 albino C57BL/6 mice were inoculated with Py8119 cells and the other 2 with saline at random. MR at 3T was performed on 8 mice before and 2-3 minutes after 0.1mmol/kg gadobutrol and on 8 mice 24-hours after 0.036mmol/kg Gd of ACPPD-Gd on days 4, 9, and 14 after inoculation. T1w tumor signal was normalized to adjacent muscle and compared between agents and the non-contrast groups using analysis-of-variance. Experienced and trainee blinded readers assessed for the presence of tumor in each of the 4 breast regions. ROC curves were constructed and the area-under-the-ROC curve (AUC) calculated.

Mouse mammary tumors imaged by MR at 3T 24 hours after ACPPD-Gd showed significantly greater T1w signal compared to tumors imaged 2-3 minutes after gadobutrol (1.57±0.2 vs. 1.25±0.13, p5mm3) were removed from the ROC analysis for the experienced observer (0.96 vs. 0.86, p=0.098), and more so for the trainee (0.86 vs. 0.69, p=0.04).

ACPPD-Gd results in significantly more T1w signal in tumors compared to gadobutrol at 3T, resulting in increased conspicuity and improved detection for experienced and more so less experienced observers.

ACPPD-Gd improves tumor conspicuity, the performance of the less experienced observers, and may highlight early stage tumors that could be missed on T1w MR imaging at clinically relevant fields strengths and scan times.

Malone, C, Olson, E, Mattrey, R, Nashi, N, Jiang, T, Ellies, L, Tsien, R, Nguyen, Q, Tumor Detection with Activatable Cell Penetrating Peptide Dendrimers (ACPPD-Gd) versus Conventional Gadolinium Chelates at 3 Tesla.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14005368.html